Day # 169: Nicotine Use Disorder
- Marcus Hunt
- 1 day ago
- 7 min read
Today we will discuss nicotine use disorder. We will cover the neurobiology, epidemiology, clinical presentation, and evidence-based treatment strategies.
Today's Content Level: Intermediate to Advanced
Introduction 1
Intro
Nicotine use disorder is one of the most common, and most underestimated, substance use disorders in society.
It is legal, socially tolerated, aggressively marketed, and extraordinarily addictive.
While cigarettes get most of the attention, modern nicotine use increasingly comes from vapes, pods, pouches, gum, lozenges, and patches and often at doses that exceed traditional smoking.
Nicotine rarely causes acute intoxication requiring hospitalization, but it drives chronic dependence, relapse cycles, and long-term morbidity.
Mechanism of Action
Nicotine is a nicotinic acetylcholine receptor (nAChR) agonist, with its reinforcing effects primarily mediated through:
α4β2 nicotinic receptors in the mesolimbic dopamine system
Rapid activation of the ventral tegmental area → release dopamine → stimulation of nucleus accumbens (behavior reinforcement hub = habit formation)
Additional effects:
Increased norepinephrine → alertness, appetite suppression
Increased acetylcholine → attention, memory
Increased beta-endorphins → mild anxiolysis
Key concept: Speed matters. Inhaled nicotine (cigarettes, vaping) hits the brain in seconds → higher addiction potential than slower delivery systems.
Diagnostic Criteria 2
Diagnostic criteria for all substance use disorders are the same, characterized by a ≥ 12-month period of problematic substance use that leads to impairment or distress and requires ≥2 additional criteria. See Day #160: Introduction to Substance Use Disorders for complete diagnostic criteria and severity specifiers.
Genetics, environmental influences, and mental health comorbidities contribute to vulnerability.
~20% of adults in the U.S. currently use nicotine in some form
Cigarette use is declining; vaping and oral nicotine are rising, especially among adolescents and young adults
It is the leading cause of preventable death in the U.S., responsible for over 480,000 deaths per year in the U.S. alone.
Genetic heritability: ~50–60%
Psychiatric risk factors: smoking 70-85% smoking prevalence in schizophrenia, 50-70% in bipolar disorder, and 75-97% comorbidity with other substance use disorders.
Other risk factors: male, younger age (most users begin before age 18), lower education and lower income, American Indian / Alaska Native ethnicity.
Pathogenesis highlights:
Repeated exposure → nicotinic receptor upregulation
Baseline dopamine tone decreases → nicotine needed to feel “normal”
Withdrawal symptoms (irritability, anxiety, dysphoria) reinforce continued use
Behavioral conditioning (coffee, driving, stress) becomes as powerful as the drug itself. Use becomes automatic, more of a reflex than a choice. At that point, nicotine isn’t creating pleasure, it’s preventing discomfort.
General SUD History
Obtain a detailed history (onset, frequency, quantity, last use, forms and routes), prior treatment attempts, periods of sobriety, withdrawal symptoms, impact on daily functioning, social history with triggers, legal obligations, and co-occurring psychiatric or medical conditions. Ask DSM-5 symptoms of SUD (loss of control, craving, risky use, tolerance, withdrawal, impairment). Ask about prescription misuse and illicit use. Ask about injection drug use, overdose history, co-use of other substances. Assess for other safety concerns related to use, including IV/IN use, sharing paraphernalia, needle licking, exchanging sex for drugs, body packing/stuffing, or impaired driving.
Nicotine Specific History
Formulations: cigarettes, cigars, pipes, water pipe (hookah, shisha), chewing tobacco, dry snuff (pinch, dip), snus, vapes, pods (e.g., JUULs), E-cigarettes (and E-hookahs, cigars, pipes), pouches, lozenges/tablets, strips/films, patches, lollipops, straws. Newer delivery systems, such as vaping, can deliver equal or higher nicotine doses than cigarettes.
Nicotine “calms anxiety” primarily because it treats withdrawal, not because it’s anxiolytic
Patients often underreport use for a variety of psychological, social, or practical reasons. Examples include → fear of judgement; desire to avoid being lectured by health professionals; lack of understanding of what constitutes a nicotine product or how to accurately track how much they consume; denial of the significance of the problem; fear of cessation/withdrawal/relapse.
Nicotine worsens a number of important health conditions: insomnia, anxiety, GERD, COPD, coronary artery disease, stroke, lung cancer, and linked to a number of other cancers as well.
Physical findings in chronic cigarette use: HTN, tachycardia, tachynpea, chronic cough, cigarette odor (hair, clothes, breathe), yellow discoloration of teeth + nails, dry skin, hair loss/thinning.
Treating nicotine use improves outcomes in depression and anxiety, not worsens them.
Be aware of drug interactions: tobacco smoke is a potent inducer of cytochrome P450 enzymes, particularly CYP1A2.
Medications metabolized via this pathway (e.g., notable = clozapine & olanzapine, minor = chlorpromazine, fluphenazine, haloperidol, methadone) may require higher doses to achieve therapeutic effects while keeping in mind if a patient quits smoking it may require decreasing the dose to prevent toxicity.
CYP1A2 induction is driven by combustion products in smoke, not by nicotine itself. Switching to vapes, pouches, or patches removes this induction, which can increase plasma levels of CYP1A2 substrates.
Intoxication
Symptoms
Usually mild, but can be clinically relevant:
Nausea, vomiting
Dizziness, headache
Palpitations, hypertension
Tremor
Anxiety or agitation
Severe toxicity (rare, usually secondary to ingestion):
Biphasic symptom pattern
Initial symptoms include nausea, vomiting, abdominal pain, dizziness, headache, tachyarrhythmias, and hypertension.
Later symptoms may include bradycardia, hypotension, lethargy, seizures, muscular weakness or paralysis, or coma.
Treatment of Intoxication
Supportive care is primary
Antiemetics as needed
Activated charcoal only in large, recent ingestions
Symptoms typically resolve within hours
Withdrawal
Symptoms:
Begins within 2–4 hours, peaks at 2–3 days, lasts 2–4 weeks
Irritability, anger
Anxiety, restlessness
Depressed mood
Insomnia
Increased appetite and weight gain
Poor concentration
Strong cravings
Treatment:
Nicotine replacement therapy (NRT) dramatically reduces withdrawal
Normalize symptoms: "this is your brain recalibrating"
•Effective treatment requires a combination of medical, psychological, and social interventions. A multi-disciplinary team—often including psychiatrists, primary care providers, therapists, social workers, and peer support specialists collaborates to address all aspects of the disorder.
Determine the Appropriate Treatment Setting: Choosing the right level of care depends on substance use severity, comorbid conditions, and prior treatment history. See Day 60: Intro to SUD for a description of each level of care.
Psychosocial Interventions:
General SUD treatment: Individual and/or group therapy should be part of every SUD treatment approach. See Day 60: Intro to SUD for a discussion of interventions that include behavioral therapies, peer support & 12-step programs, and family support resources.
Nicotine specific treatment:
Proactive counseling including individual, group therapy, and telephone/texting/app-based quitlines.
Motivational interviewing; Trigger identification; Delay-distract-decide strategies; 5 A’s (Ask, Advise, Assess, Assist, Arrange).
Setting a quit date. Be specific and near-term.
Cue-Restricted Smoking: technique that restricts smoking to specific, less-rewarding contexts, which can be combined with medication to aid cessation.
Medications:
Best outcomes come from behavioral support + pharmacotherapy. Combining behavioral interventions with nicotine replacement therapy (NRT) or medications can increase successful abstinence by up to 200% compared to no treatment.
First-line medications = Nicotine Replacement Therapy, Varenicline, and Bupropion.
Nicotine Replacement Therapy (NRT)
Long-acting patch (baseline) + gum or lozenge ( for breakthrough cravings).
Nasal spray or inhaler (less commonly used).
Combination therapy is more effective than monotherapy.
Higher dependence = more than 10-20 cigarettes per day; “all day” vaping; first hit within minutes of waking; ≥5% nicotine pod systems (JUUL, disposables)
Start with high dose patch (e.g., 21 mg) + 4 mg gum/lozenge q1-2h PRN.
Lower dependence = less than 10 cigarettes per day.
Start with lower dose patch (e.g., 14 mg) + 2 mg gum/lozenge q1-2h PRN.
Adjustments/Taper
If cravings persist or withdrawal symptoms are experienced, adjustments to the NRT regimen may be necessary, such as increasing the patch strength (or adding additional patches [off-label but common] or adding/increasing short-acting NRT.
A gradual reduction in NRT dosage over several weeks is a common approach.
Example schedule
Patch: Start patch ~4 weeks before quit date → after ~6-8 weeks step down to lower dose → continue lowering dose every ~2-4 weeks until discontinuation.
Gum: Gradually reduce the dose / increase the time between uses / decrease the number of uses per day.
Other comments: Sleep disturbances (insomnia or vivid dreams) potentially related to the patch may be managed by removing the patch before bedtime.
Varenicline (i.e., Chantix)
Partial agonist (competitive blockade) at α4β2 nicotinic receptors
Reduces cravings and reward
Start: 1 week before quit date if a quit date is planned. Stop smoking 8-35 days after starting if a quit date is unplanned.
Duration: 12 weeks (can continue additional 12 weeks)
Take with food to limit nausea.
Neuropsychiatric side effects are possible but rare and overblown. Possibilities include insomnia or vivid dreams, agitation, or depressed mood. Initially flagged by a black box warning for the potential for increased suicidal ideation, but large meta-analyses have found no significant association compared to other smoking cessation methods. Can be used in stable psychiatric illness.
Patients with serious mental illness (SMI): Consider maintenance therapy in patients with SMI. One year maintenance treatment tripled abstinence rates at one year in smokers with SMI. Also, consider starting 4 weeks in advance of proposed quit date (compared to 1 week in advance of general population).
Bottom line: Varenicline is the most effective single agent for nicotine use disorder.
Bupropion SR (Zyban, Wellbutrin) (XL is off-label)
Norepinephrine/dopamine reuptake inhibition, helping to mimic the rewarding effects of nicotine as well as maintain mood stability during the stressful (psychologically and physiologically) process of nicotine withdrawal. It also acts as a mild antagonist at nicotinic acetylcholine receptors.
Reduces withdrawal dysphoria, nicotine cravings, and pleasure from nicotine use.
Blunts weight gain that is common after nicotine cessation.
Helpful if comorbid depression or ADHD.
Start: 1-2 weeks before quit date.
Duration: 7-12 weeks (or longer if mood benefit)
Avoid in seizure disorders, eating disorders, heavy alcohol withdrawal.
Bottom line: Bupropion is less effective for smoking cessation compared to Varenicline, but wins in specific comorbid contexts -> cessation + mood/attention/weight management.
Conclusion
Nicotine use disorder is a highly reinforced neurobiological addiction with enormous public health consequences. The good news is that we understand it well, have effective treatments, and quitting meaningfully improves physical and mental health.
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